Detalhes do Documento

Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine

Autor(es): Patrício, Patrícia ; Mateus-Pinheiro, António ; Machado-Santos, Ana Rita ; Alves, Nuno Dinis Lopes Oliveira ; Correia, Joana Sofia Silva ; Morais, Mónica ; Peixoto, João Miguel Seiça Bessa ; Rodrigues, Ana João ; Sousa, Nuno ; Pinto, Luísa

Data: 2021

Identificador Persistente: https://hdl.handle.net/1822/75842

Origem: RepositóriUM - Universidade do Minho

Projeto/bolsa: info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F01079%2F2014%2FCP1212%2FCT0017/PT; info:eu-repo/grantAgreement/FCT/CEEC IND 3ed/2020.02855.CEECIND%2FCP1600%2FCT0006/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50026%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50026%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50026%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50026%2F2020/PT; info:eu-repo/grantAgreement/EC/H2020/101003187/EU;

Assunto(s): Unpredictable chronic mild stress; Depression; Antidepressants; Hippocampal cytogenesis; Cell cycle; Science & Technology


Descrição

Changes in adult hippocampal cell proliferation and genesis have been largely implicated in depression and antidepressant action, though surprisingly, the underlying cell cycle mechanisms are largely undisclosed. Using both an in vivo unpredictable chronic mild stress (uCMS) rat model of depression and in vitro rat hippocampal-derived neurosphere culture approaches, we aimed to unravel the cell cycle mechanisms regulating hippocampal cell proliferation and genesis in depression and after antidepressant treatment. We show that the hippocampal dentate gyrus (hDG) of uCMS animals have less proliferating cells and a decreased proportion of cells in the G2/M phase, suggesting a G1 phase arrest; this is accompanied by decreased levels of cyclin D1, E, and A expression. Chronic fluoxetine treatment reversed the G1 phase arrest and promoted an up-regulation of cyclin E. In vitro, dexamethasone (DEX) decreased cell proliferation, whereas the administration of serotonin (5-HT) reversed it. DEX also induced a G1-phase arrest and decreased cyclin D1 and D2 expression levels while increasing p27. Additionally, 5-HT treatment could partly reverse the G1-phase arrest and restored cyclin D1 expression. We suggest that the anti-proliferative actions of chronic stress in the hDG result from a glucocorticoid-mediated G1-phase arrest in the progenitor cells that is partly mediated by decreased cyclin D1 expression which may be overcome by antidepressant treatment.

This research was funded by FCT (grant number IF/01079/2014 and 2020.02855.CEECIND to LP) and the Nature Research Award for Driving Global Impact-2019 Brain Sciences (to LP); the Life and Health Sciences Research Institute (ICVS); FEDER, through the Competitiveness Internationalization Operational Program (POCI); National funds through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020; the projects NORTE-01- 0145-FEDER-000013 and NORTE-01-0145-FEDER-000023.; the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145- FEDER-022122); National funds through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. Part of this work was also funded by “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR20/52400020; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 101003187).

Tipo de Documento Artigo científico
Idioma Inglês
Contribuidor(es) Universidade do Minho
Licença CC
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